GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity
Top Cited Papers
Open Access
- 6 February 2014
- journal article
- Published by American Society of Hematology in Blood
- Vol. 123 (6), 809-821
- https://doi.org/10.1182/blood-2013-07-515528
Abstract
Haploinsufficiency of the hematopoietic transcription factor GATA2 underlies monocytopenia and mycobacterial infections; dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency; familial myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML); and Emberger syndrome (primary lymphedema with MDS). A comprehensive examination of the clinical features of GATA2 deficiency is currently lacking. We reviewed the medical records of 57 patients with GATA2 deficiency evaluated at the National Institutes of Health from January 1, 1992, to March 1, 2013, and categorized mutations as missense, null, or regulatory to identify genotype-phenotype associations. We identified a broad spectrum of disease: hematologic (MDS 84%, AML 14%, chronic myelomonocytic leukemia 8%), infectious (severe viral 70%, disseminated mycobacterial 53%, and invasive fungal infections 16%), pulmonary (diffusion 79% and ventilatory defects 63%, pulmonary alveolar proteinosis 18%, pulmonary arterial hypertension 9%), dermatologic (warts 53%, panniculitis 30%), neoplastic (human papillomavirus+ tumors 35%, Epstein-Barr virus+ tumors 4%), vascular/lymphatic (venous thrombosis 25%, lymphedema 11%), sensorineural hearing loss 76%, miscarriage 33%, and hypothyroidism 14%. Viral infections and lymphedema were more common in individuals with null mutations (P = .038 and P = .006, respectively). Monocytopenia, B, NK, and CD4 lymphocytopenia correlated with the presence of disease (P < .001). GATA2 deficiency unites susceptibility to MDS/AML, immunodeficiency, pulmonary disease, and vascular/lymphatic dysfunction. Early genetic diagnosis is critical to direct clinical management, preventive care, and family screening.Keywords
This publication has 57 references indexed in Scilit:
- Comprehensive molecular portraits of human breast tumoursNature, 2012
- Adult-Onset Immunodeficiency in Thailand and TaiwanNew England Journal of Medicine, 2012
- Regulation of GATA4 Transcriptional Activity in Cardiovascular Development and DiseasePublished by Elsevier BV ,2012
- Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemiaNature Genetics, 2011
- Genetic framework for GATA factor function in vascular biologyProceedings of the National Academy of Sciences, 2011
- The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiencyThe Journal of Experimental Medicine, 2011
- Gata4 directs development of cardiac-inducing endoderm from ES cellsDevelopmental Biology, 2010
- Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemiaProceedings of the National Academy of Sciences, 2008
- GATA3 haplo-insufficiency causes human HDR syndromeNature, 2000
- Transcription factor GATA-3 is required for development of the T-cell lineageNature, 1996